SelenoDB 2.0: annotation of selenoprotein genes in animals and their genetic diversity in humans

Abstract

SelenoDB (http://www.selenodb.org) aims to provide high-quality annotations of selenoprotein genes, proteins and SECIS elements. Selenoproteins are proteins that contain the amino acid selenocysteine (Sec) and the first release of the database included annotations for eight species. Since the release of SelenoDB 1.0 many new animal genomes have been sequenced. The annotations of selenoproteins in new genomes usually contain many errors in major databases. For this reason, we have now fully annotated selenoprotein genes in 58 animal genomes. We provide manually curated annotations for human selenoproteins, whereas we use an automatic annotation pipeline to annotate selenoprotein genes in other animal genomes. In addition, we annotate the homologous genes containing cysteine (Cys) instead of Sec. Finally, we have surveyed genetic variation in the annotated genes in humans. We use exon capture and resequencing approaches to identify single-nucleotide polymorphisms in more than 50 human populations around the world. We thus present a detailed view of the genetic divergence of Sec- and Cys-containing genes in animals and their diversity in humans. The addition of these datasets into the second release of the database provides a valuable resource for addressing medical and evolutionary questions in selenium biology.

Figure 1.

Human glutathione peroxidase 1 (GPx1) transcript. Note the non-synonymous, synonymous and non-coding SNPs annotated in the transcript sequence. The gene structure and transcript sequence is shown in forward despite being annotated in the reverse strand of the reference human genome.

Figure 2.

Lizard selenoprotein I (SelI). Note the predicted Sec (U) in the protein sequence as well as the TAA (#) termination codon. The N-terminal of the protein is missing due to lack of sequence similarity between the protein sequence profile used by Selenoprofiles and a divergent lizard genome sequence.

Figure 3.

Variant report for a non-synonymous (Y to H) SNP in the human GPx6 gene. An ancestral T (present in the genome of the ancestor of humans and chimpanzees) has mutated to C in humans reaching higher frequencies in some African populations. Populations are grouped according to their geographical region of origin.